Diagnosis of disease and determination of treatment efficacy are important tools in medicine. IgE antibody production in an animal can be indicative of disease including, for example, allergy, atopic disease, hyper IgE syndrome, internal parasite infections and B cell neoplasia. In addition, detection of IgE production in an animal following a treatment is indicative of the efficacy of the treatment, such as when using treatments intended to disrupt IgE production.
Immunological stimulation can be mediated by IgE antibodies when IgE complexes with Fc epsilon receptors. Fc epsilon receptors are found on the surface of certain cell types, such as mast cells. Mast cells store biological mediators including histamine, prostaglandins and proteases. Release of these biological mediators is triggered when IgE antibodies complex with Fc epsilon receptors on the surface of a cell. Clinical symptoms result from the release of the biological mediators into the tissue of an animal.
Until the discovery of the present invention, detection of IgE in samples obtained from animals has been hindered by the absence of suitable reagents for detection of IgE. Various compounds have been used to detect IgE in IgE-containing compositions. In particular, antibodies that bind selectively to epsilon idiotype antibodies (i.e., anti-IgE antibodies) have been used to detect IgE. These anti-IgE antibodies, however, can cross-react with other antibody idiotypes, such as gamma isotype antibodies. Also, creation of reagents capable of inhibiting the activity of Fc epsilon receptors has been limited.
The discovery of the present invention includes a novel feline Fc epsilon receptor alpha chain (FC.epsilon.R.alpha.) protein and the use of such a protein to detect the presence of IgE in a putative IgE-containing composition; to identify inhibitors of biological responses mediated by a feline Fc.epsilon.R.alpha. protein; and as a therapeutic compound to prevent or treat clinical symptoms that result from feline Fc.epsilon.R.alpha.-mediated biological responses. When used in an assay to detect IgE, a feline Fc.epsilon.R.alpha. protein provides an advantage over, for example anti-IgE antibodies, to detect IgE because a feline Fc.epsilon.R.alpha. protein can bind to an IgE with more specificity (i.e., less idiotype cross-reactivity) and more sensitivity (i.e., affinity) than anti-IgE binding antibodies.
Prior investigators have disclosed the nucleic acid sequence for: the human Fc.epsilon.R alpha chain (Kochan et al., Nucleic Acids Res. 16:3584, 1988; Shimizu et al., Proc. Natl. Acad. Sci. USA 85:1907-1911, 1988; and Pang et al., J. Immunol. 151:6166-6174, 1993); the human Fc.epsilon.R beta chain (Kuster et al., J. Biol. Chem. 267:12782-12787, 1992); the human Fc.epsilon.R gamma chain (Kuster et al., J. Biol. Chem. 265:6448-6452, 1990); and the canine Fc.epsilon.R alpha chain (GenBank.TM. accession number D16413). Although the subunits of human Fc.epsilon.R have been known as early as 1988, they have never been used to identify a feline Fc.epsilon.R. Similarly, even though the canine Fc.epsilon.R chain has been known since 1993, it has never been used to identify a feline Fc.epsilon.R. Moreover, the determination of human and canine Fc epsilon receptor sequences does not indicate, suggest or predict the cloning of a novel Fc.epsilon.R.alpha. gene from a different species, in particular, from a feline species.
Thus, products and processes of the present invention are needed in the art that will provide specific detection of IgE and treatment of Fc epsilon receptor-mediated disease.